microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy
Han Dong,1 Bin Dong,1 Na Zhang,2 Songyan Liu,3 Huiying Zhao1 1Department of Geriatric Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Electrical Diagnosis, Jilin Province FAW General Hospital, Changchun, Jilin P...
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oai:doaj.org-article:819b05184c634e61bd77dd5dd3b63bfb2021-12-02T09:54:49ZmicroRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy1178-2021https://doaj.org/article/819b05184c634e61bd77dd5dd3b63bfb2020-01-01T00:00:00Zhttps://www.dovepress.com/microrna-182-negatively-influences-the-neuroprotective-effect-of-apeli-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Han Dong,1 Bin Dong,1 Na Zhang,2 Songyan Liu,3 Huiying Zhao1 1Department of Geriatric Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Electrical Diagnosis, Jilin Province FAW General Hospital, Changchun, Jilin Province 130021, People’s Republic of China; 3Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Huiying ZhaoDepartment of Geriatric Medicine, The First Hospital of Jilin University, Changchun 130021, People’s Republic of ChinaTel +86-431-88783239Fax +86-431-88786439Email zhaohuiyingjdyy@126.comSongyan LiuDepartment of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86-431-84595348Fax +86-431-84596133Email songyanliujilin@163.comPurpose: To explore the neuroprotective effects and mechanisms of Apelin (APLN), and to study the regulation of APLN expression by microRNA (miRNA) in epilepsy.Materials and Methods: In vitro and in vivo epileptic models were established with hippocampal neurons and Wistar rats. Apoptosis of neurons was identified by flow cytometry. Western blotting was used to detect the expression of proteins, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to analyze the expression of miRNA and messenger RNA (mRNA). Bioinformatics software was used to predict target genes of miRNA, which were confirmed by dual-luciferase reporter gene system and functional experiments.Results: Our study demonstrated protective effects of APLN against neuronal death in epilepsy both in vitro and in vivo. The underlying mechanisms involved are inhibiting the expression of metabotropic glutamate receptor 1 (mGluR1), Bax, and caspase-3; promoting the expression of Bcl-2; and increasing phosphorylated-AKT (p-AKT) levels in neurons. For the first time, we found that miR-182 could negatively regulate both transcriptional and translational levels of APLN, and that the up-regulation of miR-182 inhibited the expression of APLN and Bcl-2, and promoted the expression of Bax and caspase-3.Conclusion: APLN could protect the neurons from injury in epilepsy by regulating the expression of apoptosis-associated proteins and mGluR1 and increasing p-AKT levels, which were attenuated by miR-182. Hence, miR-182/APLN may be potential targets for epilepsy control and treatment.Keywords: epilepsy, apelin, neuroprotective effects, miR-182, regulationDong HDong BZhang NLiu SZhao HDove Medical Pressarticleepilepsyapelinneuroprotective effectsmir-182regulationNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 327-338 (2020) |
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epilepsy apelin neuroprotective effects mir-182 regulation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
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epilepsy apelin neuroprotective effects mir-182 regulation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Dong H Dong B Zhang N Liu S Zhao H microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy |
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Han Dong,1 Bin Dong,1 Na Zhang,2 Songyan Liu,3 Huiying Zhao1 1Department of Geriatric Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Electrical Diagnosis, Jilin Province FAW General Hospital, Changchun, Jilin Province 130021, People’s Republic of China; 3Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Huiying ZhaoDepartment of Geriatric Medicine, The First Hospital of Jilin University, Changchun 130021, People’s Republic of ChinaTel +86-431-88783239Fax +86-431-88786439Email zhaohuiyingjdyy@126.comSongyan LiuDepartment of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86-431-84595348Fax +86-431-84596133Email songyanliujilin@163.comPurpose: To explore the neuroprotective effects and mechanisms of Apelin (APLN), and to study the regulation of APLN expression by microRNA (miRNA) in epilepsy.Materials and Methods: In vitro and in vivo epileptic models were established with hippocampal neurons and Wistar rats. Apoptosis of neurons was identified by flow cytometry. Western blotting was used to detect the expression of proteins, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to analyze the expression of miRNA and messenger RNA (mRNA). Bioinformatics software was used to predict target genes of miRNA, which were confirmed by dual-luciferase reporter gene system and functional experiments.Results: Our study demonstrated protective effects of APLN against neuronal death in epilepsy both in vitro and in vivo. The underlying mechanisms involved are inhibiting the expression of metabotropic glutamate receptor 1 (mGluR1), Bax, and caspase-3; promoting the expression of Bcl-2; and increasing phosphorylated-AKT (p-AKT) levels in neurons. For the first time, we found that miR-182 could negatively regulate both transcriptional and translational levels of APLN, and that the up-regulation of miR-182 inhibited the expression of APLN and Bcl-2, and promoted the expression of Bax and caspase-3.Conclusion: APLN could protect the neurons from injury in epilepsy by regulating the expression of apoptosis-associated proteins and mGluR1 and increasing p-AKT levels, which were attenuated by miR-182. Hence, miR-182/APLN may be potential targets for epilepsy control and treatment.Keywords: epilepsy, apelin, neuroprotective effects, miR-182, regulation |
format |
article |
author |
Dong H Dong B Zhang N Liu S Zhao H |
author_facet |
Dong H Dong B Zhang N Liu S Zhao H |
author_sort |
Dong H |
title |
microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy |
title_short |
microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy |
title_full |
microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy |
title_fullStr |
microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy |
title_full_unstemmed |
microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy |
title_sort |
microrna-182 negatively influences the neuroprotective effect of apelin against neuronal injury in epilepsy |
publisher |
Dove Medical Press |
publishDate |
2020 |
url |
https://doaj.org/article/819b05184c634e61bd77dd5dd3b63bfb |
work_keys_str_mv |
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